Aminotransferase Research Articles

How to identify and characterize novel transaminases? Two novel transaminases with opposite enantioselectivity for the synthesis of optically active amines

Amine transaminases (TAs) are attractive biocatalysts for the synthesis of chiral aromatic amines representing highly valuable motifs of APIs. The increased industrial need of novel methods to produce chiral amines for APIs resulted in an emerged discovery of new TAs. Joining the current wave of TA related research, this study reports the identification of genes encoding an (S)-selective TA from Pseudomonas psychrotolerans TA (PpS-TA) and an (R)-selective TA from Shinorizobium sp. TA (SrR-TA) by sequence data mining. Functional analysis of the novel TAs revealed their pH profile, thermal stability, optimal buffer system, DMSO tolerance, and operational stability in kinetic resolution (KR) of racemic 1-phenylethane-1-amines. The (S)-selective PpS-TA maintained its operational stability even at high temperature and pH values, enabling conversions from racemates approaching the optimal ∼50% value of a highly selective KR. Although with lower activity, the (R)-selective SrR-TA remained active at higher DMSO co-solvent concentrations up to 30%, enabling elevated substrate concentrations for aromatic amines of low water-solubility. The kinetic parameters of the novel PpS-TA and SrR-TA in KRs of several racemic 1-arylethane-1-amines (±)-2a-d and pyruvate (co-substrate) revealed superior catalytic efficiencies (kcat values) compared to the well-characterized (S)-TA from Chromobacterium violaceum (CvS-TA) indicating the biocatalytic potential of the two newly characterized TAs.

The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects.

It is well known that the enzyme catalyzes the first step of branched-chain amino acid (BCAA) catabolism is branched-chain amino transferase (BCAT), which is involved in the synthesis and degradation of leucine, isoleucine and valine. There are two main subtypes of human branched chain amino transferase (hBCAT), including cytoplasmic BCAT (BCAT1) and mitochondrial BCAT (BCAT2). In recent years, the role of BCAT in tumors has attracted the attention of scientists, and there have been continuous research reports that BCAT plays a role in the tumor, Alzheimer’s disease, myeloid leukaemia and other diseases. It plays a significant role in the growth and development of diseases, and new discoveries about this gene in some diseases are made every year. BCAT usually promotes cancer proliferation and invasion by activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway and activating Wnt/β-catenin signal transduction. This article reviews the role and mechanism of BCAT in different diseases, as well as the recent biomedical research progress. This review aims to make a comprehensive summary of the role and mechanism of BCAT in different diseases and to provide new research ideas for the treatment, prognosis and prevention of certain diseases.

The Anti-obesity Effect of Allium cepa L. leaves on High Fat Diet Induced Obesity in Male Wistar Rats

Over the years, there has been research on the anti-obesity effect of the Allium cepa bulb, but a dearth of research was carried out on the leaves, which is consumed as vegetable salad and soup, hence this study was proposed. This study aims at investigating the effect of A. cepa leaves on high fat diet (HFD) induced obesity in male Wistar rats. Twenty-eight male Wistar rats were divided into four groups with seven rats each. Apart from Group 1 (normal control which received normal pelleted diet), obesity was induced in 21 rats of Group 2 to 4 with HFD. Group 2, the obese control was administered with 100% HFD, while the diet for group 3 and 4 was supplemented with 10% and 20% A. cepa powdered leaves, respectively, for 28 days. In the rats treated with 10% and 20% A. cepa , body weight, fat mass, blood glucose, total cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase, creatinine and urea levels were reduced significantly ( P < 0.05) in comparison with the obese control group. The liver of the rats treated with 10% and 20% A. cepa leaves revealed small and few amounts of fat deposits in comparison with the obese control group, which revealed numerous and large deposits of fat. The kidney of the rats treated with 10% and 20% A. cepa leaves showed moderate and mild inflammation, respectively, in comparison with the obese control group which showed acute inflammation. The leaves of A. cepa had antioxidant properties and the presence of volatile compounds with anti-obesity properties in A. cepa were identified using gas chromatography-mass spectrometry (GC-MS). A. cepa leaves had weight-loss effect in that it decreased body weight, fat mass, glucose and lipid levels including fat deposits in the liver.

Effects of dietary yeast β-1.3/1.6-glucans on oxidative stress biomarkers in hearts and livers of rainbow trout (Oncorhynchus mykiss Walbaum), European whitefish (Coregonus lavaretus L.), and grayling (Thymallus thymallus L.)

Abstract The present study was performed to investigate the effects of dietary yeast β-1,3/1,6-D-glucans supplemented over a 14-day feeding period on liver and cardiac function and the oxidative mechanism underlying these effects. We assessed relevant lipid peroxidation and protein oxidation biomarkers, antioxidant defense indices [superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), total antioxidant capacity (TAC)], and biochemical alterations [activities of aminotransferases (AT), lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH), and levels of lactate (L) and pyruvate (P)] in rainbow trout, European whitefish, and grayling. The fish received a control diet and an experimental diet containing yeast β-1,3/1,6-D-glucans at a dose of 1% in the basal feed for 14 days. The results demonstrated enhancement in the phagocytic activity and phagocytic index in the groups fed β-glucans, compared to the control groups. In the groups fed β-glucans, the oxidative stress parameters such as lipid peroxidation, oxidatively modified proteins, and TAC did not vary significantly. The dietary β-glucans stimulated CAT and GPx activities in hepatic and cardiac tissues in comparison to the control group; however, a reverse trend was observed in the GR activity in these tissues.

Evaluation of Anti Urolithiatic Activity of Dolichos biflorus Seed Extract by Using Ethylene Glycol Induced Model

In the phytochemical screening, it was found that Dolichos Biflorus seed extract contained the presence of tannins steroids, protein, flavonoids, terpenoids, mucilage, saponin, and carbohydrate, but no alkaloids fixed oil. So, this plant has highly diuretic activity. Which can use for the treatment of urolithiasis.&#x0D; Objective: The Present study aims to investigate the anti-Urolithiatic activity of Dolichos Biflorus methanolic seed extract in a rat model.&#x0D; Methods: Dolichos Biflorus Seeds Extract were evaluated for anti-Urolithiatic activity. Urolithiasis has been induced in Wistar rats through Ethylene glycol (0.75%v/v, p.o). Upon completion of the experiment, animals in all groups have been sacrificed and biochemical parameters such as; calcium, creatinine, Phosphorus, Uric acid, Alkaline Phosphatase BUN (Blood Urea Nitrogen), and histology of Kidney have been observed. Furthermore, Potassium, Oxalate levels, and Alanine Amino Transferases were measured.&#x0D; Results: The extract of Dolichos Biflorus was proven to be safe in the toxicity findings.&#x0D; It has been shown that in-vivo significant effect of plant extract was able to manage the urolithiatic markers such as calcium, creatinine, phosphorus, uric acid, alkaline phosphatase, BUN (Blood Urea Nitrogen), and potassium. In the urolithiatic rats it has been observed that abundant crystal depositions, renal epithelial cells had more tubular dilatation and damage shown by large spaces in the tissue, renal stone deposition damages the renal tissue and detoriate the renal function. Urolithiatic markers such as calcium, creatinine, phosphorus, uric acid, alkaline phosphatase, BUN (Blood Urea Nitrogen), and potassium were normal in animals receiving plant extract and prevent renal cell injury.&#x0D; Conclusion: All its findings and phytoconstituents existing inside the extract must stay the viable chemical materials involved in the prevention of Urolithiatic.

P-078: HEPATOBILIARY AND SPLENIC COMPLICATIONS OF SICKLE CELL DISEASE IN NIAMEY. A RETROSPECTIVE STUDY FROM 145 PATIENTS

Purpose: Sickle cell disease is the most widespread hereditary genetic disease in the world, particularly in black populations [1]. In Niger, there were 20% sickle cell trait and 1.8% were homozygous SS [2]. Subjects with major sickle cell disease may have serious clinical manifestations whose evolution will lead to numerous hepatobiliary and splenic complications variable in their severity and temporality. The objective of this work is to analyze the frequency and the characteristics of the hépatobiliary and splenic complications, in order to prevent them and to facilitate their taking up. Materials and methods: We led a retrospective and transverse study in the National Reference Center of sickle cell disease (CNRD) of Niamey between 2014 to 2021. The regularly followed patients were identified on the basis of medical file. On the whole 3000 files with a request of abdomino-pelvic ultrasound and hepatic enzymes had been consulted. Patients of less than 3, those of more than 50 years old and those whose medical file was incomplete are not included. Results: Approximately 4,8% patients (145 patients) presented complications to abdomino-pelvic ultrasound. The sex ratio (M/F) was of 1,15. The Average Age is 14,13 with extremes ranging from 4 to 49 years. The age bracket <10 years was more frequent (52,41%), followed by the one of 10 to 20 (27,01%). The sickle cell anemia phenotype consisted of 84,8% SS (123 cases), 14,5% of SC (21 cases) and 0,7% of Sβ° thalassaemia (1cases). The circumstances of the discovery of the disease are dominated by the splenomegaly and the vaso-occlusive crisis respectively in 22,8% and 15,2%. The hepatic enzyme aspartate amino transferase (ASAT) was high in 72,6% of the patients. The most frequent complications were hepatomegaly alone (HPM) (60,7%), followed by the hepato- splenomegaly in 17,3% and splenomegaly alone (SPM) in 9,66% of the cases. The vesicular lithiasis was found in 12,4% of the cases. The average age of patients with hepatomegaly and splenomegaly was 36,5 years old. The average age of the of onset of the lithiasis alone was 21,85 years old. Those with splenomegaly alone had an average of age younger 10,64. The average age of onset of the 3 associated complications hepatomegaly+ splenomegaly+ Lithiasis was 18,8 years old. Hyperbilirubinemia is higher among patients presenting hepatomegaly + Lithiasis, it is the same as for the hepatic enzymes. Indeed 73.79% of patients were hospitalized either because of vaso-occlusive crisis (35.42%) or anemia (21.53%). All the patients had received medical care with antibiotics, antimalarials, antispasmodics, analgesics and parenteral rehydration. Three patients had undergone cholecystectomy. Conclusion: Sickle cell disease is a serious public health problem in black african populations and major clinical findings despite anemia are liver and splenic complications which must been looked out and followed because of their morbidity and invalidity keeping home young pupils compromising their scholar education. A great carefull follow up should be done for these kind of patients. The authors do not declare any conflict of interest

An Evaluation of Yeast Culture Supplementation in the Diet of Pseudobagrus ussuriensis: Growth, Antioxidant Activity, Nonspecific Immunity, and Disease Resistance to Aeromonas hydrophila

An 8-week feeding trial was conducted to evaluate the effects of dietary yeast culture (YC) supplementation on growth performance, antioxidant activity, nonspecific immunity, and disease resistance of Pseudobagrus ussuriensis (average initial weight6.01±0.01 g). Four isonitrogenous and isolipidic diets were formulated to contain 0 (Y0), 10 (Y1), 20 (Y2), and 30 (Y3) g/kg YC, respectively. After the feeding experiment, the challenge test of injecting Aeromonas hydrophila was executed. Results showed that appropriate YC supplementation level in the diet could improve growth performance, digestive enzyme activities, nonspecific immunity capacity, antioxidant capacity, and disease resistance of P. ussuriensis. And the highest weight gain, feed intake, specific growth rate, and IGF-1 gene expression level were observed in fish fed the Y2 diet. The activities of protease and amylase in intestine in fish fed the Y2 diet were enhanced compared with that in fish fed the Y0 diet significantly (P&lt;0.05). Simultaneously, fish fed the Y2 diet had significantly higher serum lysozyme activity and significantly lower serum alanine amino transferase activity (P&lt;0.05). Dietary 20 g/kg YC supplementation increased the activity of catalase and total antioxidant capacity in liver and reduced malondialdehyde content in the liver and intestine of P. ussuriensis significantly (P&lt;0.05). Fish fed the Y2 diet had the highest disease resistance under the condition of A. hydrophila challenge (P&lt;0.05). The quadratic regression analysis based on weight gain against dietary YC levels indicated that the appropriate dietary YC supplementation level is 13.4 g/kg diet.

Assessment of hazardous impact of nickel oxide nanoparticles on biochemical and histological parameters of gills and liver tissues of Heteropneustes fossilis

BackgroundThe aim of the present study was to assess the hazardous impact of nickel oxide nanoparticles (NiO NPs) on gills and liver of Heteropneustes fossilis. MethodsFishes were treated with four concentrations of NiO NPs for a period of 14 days. Nickel accumulation, lipid peroxidation, antioxidant enzymes activities (superoxide dismutase, catalase, glutathione s transferase & glutathione reductase), liver enzymes activities (aspartate amino transferase, alanine transaminase, & alkaline phosphatase), Na+/K+ ATPase activity, FTIR, metallothionein content, ethoxyresorufin-o-deethylase activity, immunohistochemistry, histology and scanning electron microscopy were analyzed in both gills and liver tissues. ResultsResults revealed increased accumulation of nickel in both the tissues of exposed fishes. Lipid peroxidation and activities of different antioxidant enzymes increased (except superoxide dismutase) in both the tissues after exposure. Fluctuations in liver enzymes activities and variation in the activity of Na+/K+ ATPase were also observed. FTIR data revealed shift in peaks position in both the tissues. Level of metallothionein and its expression as well as activity of ethoxyresorufin-o-deethylase and expression of CYP1A also increased in both the target tissues of treated fishes. Furthermore, histological investigation and scanning electron microscopy showed structural damages in gills as well as liver tissues of exposed fishes. ConclusionOur results suggest that NiO NPs cause deteriorating effects on the gill and liver tissues of fish, therefore effluents containing these nanoparticles should be treated before their release into water bodies.

Effects of perilipin-5 on lipid metabolism and high-sensitivity cardiac troponin I.

SUMMARYOBJECTIVE:Heart attack is one of the most common causes of sudden death in adults. Therefore, early detection of heart attack and investigation of potential new biomarkers are of great importance. We investigated whether perilipin-5 is a potential biomarker by examining changes in perilipin-5 serum levels along with high-sensitivity cardiac troponin I during a heart attack.METHODS:The subjects were divided into two groups: (1) control group and (2) patients with heart attack, with 150 people in each group. High-sensitivity cardiac troponin I, perilipin-5, total oxidant status, malondialdehyde, reduced glutathione, and superoxide dismutase levels in serum samples were measured. In addition, perilipin-5 mRNA expressions and protein levels were analyzed.RESULTS:There was no overall statistical difference between the demographic characteristics of the groups. However, high-density lipoprotein, creatine kinase, Creatine kinase myocardial band, aspartate amino transferase, lactate dehydrogenase, and calcium levels were higher in the heart attack group compared to the control group. We found that the high-sensitivity cardiac troponin I and perilipin-5 levels increased in the patients with heart attack (p<0.0001) compared to control. Although there was an insignificant increase in malondialdehyde levels in the heart attack group (p>0.05), there was a 35.9% increase in total oxidant status levels and a 33.5 and 24.1% decrease in glutathione and superoxide dismutase levels, respectively (p<0.01), compared to control. Perilipin-5 mRNA and protein levels in heart attack patients increased by 48.2 and 23.6%, respectively, compared to the control group (p<0.01).CONCLUSION:Our results showed that perilipin-5 together with high-sensitivity cardiac troponin I could be a promising biomarker in heart attack.

Incidence of Diabetes in Hepatitis C Patients in Remote Areas of Pakistan: Effect of Co-Morbidity on HCV Treatment Outcomes at Selected Secondary Care Hospitals

The management of Hepatitis C (HCV) varies greatly due to co-morbidities. Association of Type II Diabetes Mellitus (T2DM) and HCV infection is momentous, however, only limited studies available from remote areas of Pakistan. This study aimed to assess the incidence of T2DM in Hepatitis C patients, and to measure the treatment outcomes of anti-HCV therapy in co-morbidity of diabetic patients in remote areas of Khyber Pakhtunkhwa Pakistan. A cross-sectional retrospective analysis of HCV patients (n=449) was conducted in the District Hospitals of Bannu and Lakki Marwat, Pakistan. Patients diagnosed of HCV infection and having T2DM as comorbidity were included in the study. The demographic information and laboratory parameters, such as viral load (VL), hemoglobin (Hb), alanine amino transferase (ALT), and platelet count were collected to measure treatment outcomes. T2DM was found in 33.18% of patients and significant association (p ? 0.05) was found with HCV infection as a co-morbidity. Sofosbuvir (SOF) and Ribavirin (RBV) therapy reduced the mean (SD) VL (x103) from baseline 357.1±26.23 IU /mL to 14±2.3 IU/mL and 1.3±0.3 IU/mL at 3rd and 6th months of therapy, respectively. Conventional Interferon and Ribavirin (RBV) therapy reduced VL from a baseline 234.57±13.5 IU/mL to 72±7.9 IU/mL and 62 ±3.7 IU/mL at 3rd and 6th months of therapy, respectively. PEG-Interferon+ Ribavirin (RBV) therapy reduced baseline VL from 337±16.27 IU/mL to 18±2.8 and 4±1 at 3rd and 6th month of therapy, respectively. Similarly, Hb, ALT, and platelet count showed variations in all the studied groups. T2DM was highly prevalent and significantly associated with HCV in patients of 40 years or above and SOF+RBV combination therapy showed a better response, both in the diabetic and non-diabetic HCV patients compared to earlier the therapies. To further confirm the finding, a study using a larger population of HCV patients with T2DM should be conducted.

Comparative effects of Moringa oleifera and ascorbic acid on biochemical changes induced by subchronic lead toxicity in male Wistar rats

This experiment was aimed at comparing the effects of Moringa oleifera (MO) and ascorbic acid (AA) on biochemical changes induced by subchronic lead (Pb) toxicity in male Wistar rats. A total of 36 adult male Wistar rats were used for the work with grouping and dosing as follows; Group I was given distilled water (2 mL) only, Group II rats were administered Pb (190 mg/kg), Group III received Pb (190 mg/kg) + MO (500 mg/kg). While rats in groups IV, V, and VI were administered Pb (190 mg/kg) + AA (100 mg/kg), Pb (190 mg/kg) + MO (500 mg/kg) + AA (100 mg/kg) and Pb (190 mg/kg) + MO (250 mg/kg) + AA (50 mg/kg) respectively. Administration of all agents was done daily by oral gavage for a period of 6 weeks. Result showed decreased alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) levels in group II compared to other groups. Creatine kinase (CK) activity was significantly (P ≤ 0.05) higher in group II compared to other groups while lactate dehydrogenase (LDH) activity was significantly decreased in group II compared to other groups. Total protein, albumin and globulin concentrations were not significantly (P ≥ 0.05) different across all groups. The malondialdehyde concentration in group 2 was higher (P < 0.001) compared to other groups. A decrease (P < 0.01) was observed in superoxide dismutase activity in group 2 compared with groups 3 and 6. There was no significant difference (P > 0.05) in catalase and glutathione peroxidase activities among groups. This study depicts the detrimental effects of Pb on biochemical parameters in the rats. Treatment with AA (50 mg/kg) and MO (250 mg/kg) gave better amelioration of the toxic effects of Pb.

Therapeutic Effect of Vernonia Amygdalina Aqueous Leaf Extract on Salmonella Typhimurium-Infected Female Wistar Rats

This study investigated the therapeutic effects of Vernonia amygdalina aqueous leaf extract administration on Salmonella typhimurium infected Wistar rats. Rats were infected orally by a single dose administration of Salmonella typhimurium (1.5 x 108 CFU). Negative control groups were infected and treated orally with vehicle (distilled water), neutral control group were not infected, while the four test groups were treated up to 24 days with 50 mg/kg. 100 mg/kg, 150 mg/kg and 200 mg/kg body weight of aqueous leaf extract of V. amygdalina respectively. The effects of leaf extract administration on serum markers (amino transferase activities, total protein, creatinine and bilirubin levels), as well as histopathology of the liver and kidney tissues were also investigated. Following in vivo studies, the 50 mg/kg dose of aqueous leaf extract of V. amygdalina was effective in alleviating liver damage as seen in the amino transferase activity. Infection resulted in a significant increase of amino transferase activity. The drug and plant extract helped to alleviate liver and kidney damage from infection as observed in the organ weights and their protein content. Findings from this study showed that the administration of this aqueous leaf extract at higher doses resulted in the ameriolation of the tissue damage caused by the S. Typhi bacteria (from histological studies). These results support the ethnomedicinal use of V. amygdalina, and posits that its leaves can be used in antibacterial phytomedicine.

Effects of Aqueous Extract of Petroselinum crispum on Liver and Hematological Parameters in Carbon Tetrachloride (CCl4) - Induced Hepatotoxicity in Male Wistar Rats

In recent years, focus on plant research has increased to show the potential of some medicinal plants in discovery of novel compounds which could be used in treatment of some diseases. Petroselinum crispum is widely used traditionally as a food additive and herbal remedy for many ailments. This study is aimed to assess the effects of Petroselinum crispum on some liver enzymes and some haematological parameters in Carbon tetrachloride (CCL4) - induced hepatotoxicity in male wistar rats. A total of 25 wistar rats were used, which were divided into 5 groups of 5 rats each. Group 1: (control); Group 2: received IP injection of 120mg/kg mixture of CCL4 and olive oil (1:1), Groups 3, 4 and 5 were orally administered 250, 500 and 1000mg/kg extract + IP injection of 120mg/kg mixture of CCL4 and olive oil for 21 days respectively. On the 22nd day, the animals were sacrifice using chloroform anesthesia and the effects of the aqueous extract were assessed by quantifying liver enzymes such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total serum protein (TP). The haematological parameters were assessed by analysis of parked cell volume (PCV), red blood cell count (RBC), white blood cells (WBC), haemoglobin (Hb) concentrations and platelet count (PLT) and followed by histopathological studies of the liver tissues. The three doses of the plant extract used in this study, showed some level of protective effect on CCL4-induced hepatotoxicity as evident by the significant reduction (P &lt; 0.05) in serum levels of AST, ALT, and ALP along with the improved histopathological liver sections compared to CCL4 -treated animals. However the extract is more effective in the 500mg/kg compared to the 250mg/kg and 1000mg/kg. Also the results obtained for all the haematological parameters used in the study showed no significant difference among all the groups (P &gt; 0.05).

Modulatory effect of Ovothiol-A on myocardial infarction induced by epinephrine in rats.

Myocardial infarction (MI) is one of the most prevalent disorders seen in clinical practice, and its prevalence has risen dramatically in the last decade. Ovothiol-A is a natural product isolated from sea urchin eggs and display unusual antioxidant properties. The present study investigates the therapeutic effect of Ovothiol-A against MI stimulated in rats by epinephrine injection. Subcutaneous injection of 2 mg/kg epinephrine for 2 days caused MI in rats. The rats divided into three groups; control, MI, and MI treated with Ovothiol-A (500 mg/kg, orally) for 7 days. The treatment with Ovothiol-A restored ST-segment near normal, ameliorated the changes in cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, total proteins, creatinine, uric acid, urea, malondialdehyde, nitric oxide, reduced glutathione, catalase, glutathione-S-transferase, hemoglobin, RBCs, WBCs, platelet/lymphocyte ratio, and neutrophil/lymphocyte ratio. The histological investigation revealed that Ovothiol-A-treated group showed marked improvement in the examined cardiac muscles, liver and kidney in numerous sections. Ovothiol-A possessed a therapeutic effect against epinephrine-induced myocardial infarction. Ovothiol-A improves cardiac, liver, and kidney biomarkers and restores the typical pattern of EEG. PRACTICAL APPLICATIONS: Eggs of sea urchins are rich in potent antioxidant molecule (Ovothiol-A). The current study reveals the ability to use Ovothiol-A in the treatment of myocardial infarction.

Muscle fatique and muscle damage in strength training

Background and Study Aim. The aim of this study is to investigate the effects of different types of contractions on muscle damage and muscle fatigue in sedentary individuals.&#x0D; Material and Methods. Thirty healthy male sedentary individuals participated in the study. Strength training in different types of contractions applied in the study was applied 3 times a week for 8 weeks. Before the study, the training loads were determined by making maximal force measurements of all subjects. The 30 subjects participating in the study were divided into 3 groups: isometric (n = 10), concentric (n = 10) and eccentric (n = 10) contraction group. Appropriate amount of blood samples was taken from the elbow vein 2 times from all subjects, before the studies and at the end of the 8-week strength training.&#x0D; Results. It was observed that eight-week strength training did not cause muscle fatigue in all groups and did not create a statistically significant difference (P&gt; 0.05). Strength training with isometric and concentric contractions for eight weeks significantly increased serum lactate dehydrogenase (LDH), C-reactive protein (CRP), myoglobin (Mb), interleukin 6 (IL-6) levels, while concentric strength training significantly reduced serum aspartate amino transferase (AST) levels. Strength training with eccentric contractions significantly increased serum LDH, CRP, AST, Mb and IL-6 levels, while significantly reducing serum tumor necrosis factor alpha (TNF-α) levels. Strength training with eccentric contractions significantly increased serum creatine kinase (CK), CRP, AST, IL-6 and Mb levels compared to strength training with isometric and concentric contractions at the end of the eight-week study period, but did not show the same significant effect in other parameters.&#x0D; Conclusions. As a result, it can be said that eccentric strength training performed in sedentary individuals leads to more muscle damage than isometric and concentric strength training.

Dietary Incorporation of Ractopamine Hydrochloride Improves Body Composition and Metabolic Enzyme Activity in Calbasu, Labeo calbasu Fingerlings, despite High- and Low-Protein-Supplemented Diet

A 60-day feeding trial was conducted to examine the effect and interaction of dietary ractopamine hydrochloride (Rac) supplementation in diets with varied levels of protein and lipid for L. calbasu fingerlings. To attain this, the fish body compositions, digestive and metabolic enzyme activity were assessed. In total, nine diets were fed in triplicates to four hundred and five healthy Calbasu, Labeo calbasu fingerlings, based on ractopamine supplementation, viz., control (0 mg/kg), T1 (10 mg/kg), and T2 (20 mg/kg). The diets were further assigned in different levels of protein and lipid, viz., 35% protein and 6% lipid, 30% protein and 9% lipid, and 25% protein and 12% lipid. At the end of the trial, it has been observed that the inclusion of ractopamine hydrochloride at 20 mg/kg-1 of basal diet significantly ( p &lt; 0.05 ) improved the protein content in fed fish compared to the control. In addition, metabolic enzyme activity for hexokinase, glucose-6-phosphate, and glucose-6-phosphate dehydrogenase along with aspartate amino transferase and alanine amino transferase activity were significantly ( p &lt; 0.05 ) improved with the inclusion of 20 mg/kg ractopamine hydrochloride. However, the supplementation of ractopamine hydrochloride does not improve ( p &gt; 0.05 ) digestive enzyme activity, viz., amylase, lipase, and protease activity in the fed fish. Conclusively, it implies that adding ractopamine hydrochloride at 20 mg/kg of basal diet (high and low protein content) enhances the whole-body protein content and improves the metabolic enzyme activity in L. calbasu fingerlings. Hence, ractopamine hydrochloride has a beneficial effect in L. calbasu fingerlings and would be a desirable feed supplement for this new species culture system.

Monitoring different causal patterns of bovine abortion syndrome

Bovine Abortion Syndrome (bas) has a significant impact on commercial dairies. Abortion rates vary between 2 and 20 % and there is little information regarding non-infectious factors affecting fetal stages. We analyzed the joint relationship of infectious and non-infectious factors with the probability of abortion in dairy cows. We used dairy cows from the Ñuble province of Chile (n = 148) at 42 days of pregnancy. We then took monthly blood samples until abortion or calving. We determined plasma concentrations for the following: amino transferase, albumin, cholesterol, globulin, fibrinogen, â-hydroxybutyrate, retinol, á-tocopherol, calcium, phosphorus, glutathione peroxidase, total proteins and urea. Serology was performed for infectious diseases and body conditions were recorded. Our study used a multivariable logistic regression model and proportional hazard regression. There was an (p &lt; 0.05) association with abortion, (or = 4.27) for Neospora caninum and (hr = 94.35) for Leptospira interrogans, with a low cholesterol concentration (p &lt; 0.05) in the fourth month of pregnancy (or = 0.61), and a decrease in body condition from month three to four (or = 0.32). bas is associated with negative energy balances, protective effects of high cholesterol plasma concentrations in the first trimester of gestation and incidences of Neospora caninum, Leptospira interrogans, and a conjunction of the two. It is important to provide epidemiological surveillance tools that help anticipate herd reproductive losses through management measures, infectious disease control and proper nutritional management.

Evaluation of TyG index and TG/HDL-C ratio in HBeAg negative chronic hepatitis B infected patients.

Patients with hepatitis B e antigen (HBeAg) negative chronic HBV infection are regularly followed up. This study investigates the presence of insulin resistance and the relationship between hepatosteatosis and insulin resistance in patients with HBeAg negative chronic HBV infection using the TyG index and TG/HDL-C ratio. Patients with HBeAg negative chronic HBV infection who applied to the Infectious Diseases and Clinical Microbiology outpatient clinic between January 2019 and December 2020 were included in the study. Glucose, lipid panel, alanine amino transferase (ALT), acetyl amino transferase (AST), body mass index (BMI), TyG index, TG/HDL-C and hepatobiliary ultrasonography (USG) results were evaluated. The data were compared with the control group consisting of 308 HBsAg negative individuals. The study included 132 patients with a median age of 52 years. There was no significant difference between the patient and control groups regarding age, gender and BMI. Glucose, total cholesterol, TG, LDL, AST, ALT, TyG index and TG/HDL-C ratio were significantly higher in patient than in the control group. At the same time, the HDL value was significantly lower in the patients. There was a strong positive correlation between the TG and BMI, and a strong negative correlation between HDL levels and both TyG index and TG/HDL-C ratio. Our findings showed that the TyG index and TG/HDL-C ratio are helpful in the diagnosis of insulin resistance and hepatosteatosis in patients with HBeAg negative chronic HBV infection.

Abstract 2179: Increased BCAT1 expression creates a pseudo-hypoxic environment that promotes cell proliferation in a subtype of glioblastoma

Abstract Background: BCAT1 (Branched Chain Amino Transferase 1) has been shown to be upregulated in human IDH (isocitrate dehydrogenase) wild-type glioblastoma (GBM) and BCAT1 knockdown leads to reduced cell proliferation in vitro and in vivo1. Here we investigated the role of BCAT1 in human patient-derived glioblastoma cells and the corresponding orthotopically implanted xenografts to understand how upregulation of the enzyme leads to a more aggressive phenotype. Methods: The expression of BCAT1 was investigated in a panel of patient derived IDH wild-type glioblastoma cells and BCAT1 expression modulation was achieved using lentiviral expression of a doxycycline-inducible shRNA, to knockdown BCAT1 and expression of a BCAT1 cDNA to overexpress BCAT1. Effects of BCAT1 knockdown and overexpression were investigated in vitro in cell culture and in vivo, following intracranial implantation of mice with the relevant cells. Results: Variable levels of BCAT1 expression were identified in different patient-derived cell lines. RNA sequencing analysis of BCAT1 knockdown in BCAT1 expressing glioblastoma cells revealed that knockdown led to significant downregulation of HIF 1α (Hypoxia Inducible Factor 1α) and its targets, which was confirmed by Western Blot analysis of Carbonic Anhydrase IX (CAIX) and Hexokinase II (HKII) in cell and tumor lysates. The opposite was observed following BCAT1 overexpression. BCAT1 knockdown also led to higher DNA demethylation levels. Treatment with membrane permeant dimethyl-alpha ketoglutarate mimicked the effect of BCAT1 knockdown. These data suggest that decreased cell proliferation following BCAT1 knockdown in BCAT1 expressing cells is mediated by accumulation of alpha-ketoglutarate, a substrate of BCAT1. Cells that had no BCAT1 expression showed a similar growth profile and overexpression had no effect on proliferation, suggesting that these cells are not dependent on BCAT1 expression. Conclusion: We conclude that in a subtype of GBM characterized by upregulated BCAT1, BCAT1 expression results in lowered levels of alpha-ketoglutarate, leading to reduced prolyl hydroxylase activity and stabilization of HIF 1α and therefore a pseudo-hypoxic state, resulting in a transcriptome that favors a high proliferation rate. This makes BCAT1 a potential therapeutic target, for tumors that show BCAT1 upregulation.1. Tönjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med. 2013;19(7):901-908. doi:10.1038/nm.3217 Citation Format: Maria Fala, Susana Ros, Ashley Sawle, Kevin M. Brindle. Increased BCAT1 expression creates a pseudo-hypoxic environment that promotes cell proliferation in a subtype of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2179.

Abstract CT554: Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced squamous (sq) non-small-cell lung cancer (NSCLC): Sub-analysis from phase 3 RATIONALE-303 randomized clinical study

Abstract Background: At a predefined interim analysis (IA), RATIONALE-303 (NCT03358875) demonstrated improved overall survival (OS) for TIS vs D in the intent-to-treat (ITT) population with a manageable safety profile. Given disease characteristics, standard of care treatment/prognosis differ between histologic types of NSCLC. Here we report the data on the sq population. Methods: 805 patients (pts) with histologically confirmed, advanced NSCLC with progressive disease during or after ≥ 1 platinum (Pt)-containing chemotherapy regimen were randomized (2:1) to TIS 200 mg IV or D 75 mg/m2 IV every 3 weeks until disease progression, intolerable toxicity, or withdrawal. Histology (sq vs non-sq), was a stratification factor for randomization. Dual primary endpoints were OS in the ITT and PD-L1 ≥ 25% populations. The IA was conducted after ~426 deaths (76% of planned events). Efficacy and safety were assessed in 370 randomized pts with sq histology. Results: Baseline characteristics of sq pts were balanced between treatment arms and similar to the ITT population. As of August 10, 2020, at median follow-up of 19.0 and 19.3 months (mo), respectively, median (95% CI) OS was longer with TIS (16.0 mo [13.8, 18.9]) vs D (11.3 mo [8.7, 12.7]) in the sq ITT population, and progression free survival (PFS), objective response rate (ORR) and duration of response (DoR) were also improved for TIS vs D (Table). 95.1% (TIS) and 99.1% (D) of pts had ≥ 1 treatment-emergent adverse event (TEAE) and 38.1% (TIS) and 79.5% (D) of pts had ≥ Grade 3 TEAEs. The most common TEAEs were anemia, cough and alanine amino transferase increased (TIS arm), and anemia, alopecia, and neutrophil count decreased (D arm). Conclusions: TIS prolonged OS with a favorable safety profile in pts with advanced sq NSCLC who progressed after a Pt-containing regimen. The data are consistent with the overall ITT population. Efficacy* TIS (n=248) D (n=122) Median OS, mo (95% CI) 16.0 (13.80, 18.86) 11.3 (8.67, 12.68) OS HR (95% CI)† 0.58 (0.436, 0.761) P &amp;lt; 0.0001‡§ Median PFS, mo (95% CI) 6.2 (4.21, 6.37) 2.3 (2.10, 3.38) PFS HR (95% CI)† 0.45 (0.343, 0.577) P &amp;lt; 0.0001‡§ ORR, n (%) 57 (23.0) 5 (4.1) Median DoR, mo (95% CI) 16.7 (8.31, NE) 6.2 (2.10, 8.31) Safety** TIS (n=247) D (n=117) TEAEs ≥ 20% of patients in either arm, n (%) All grades ≥ Grade 3 All grades ≥ Grade 3 Anemia 76 (30.8) 7 (2.8) 56 (47.9) 10 (8.5) Decreased appetite 41 (16.6) 2 (0.8) 33 (28.2) 3 (2.6) Asthenia 38 (15.4) 5 (2.0) 27 (23.1) 6 (5.1) White blood cell count decreased 12 (4.9) 1 (0.4) 32 (27.4) 21 (17.9) Leukopenia 9 (3.6) 1 (0.4) 31 (26.5) 19 (16.2) Neutrophil count decreased 7 (2.8) 2 (0.8) 42 (35.9) 35 (29.9) Alopecia 5 (2.0) 0 (0.0) 52 (44.4) 0 (0.0) Neutropenia 2 (0.8) 0 (0.0) 37 (31.6) 34 (29.1) *Efficacy analysis set - Sq patients; †Stratified; ‡One-sided stratified log-rank test; §Descriptive P-value; **Safety analysis set - Sq patients CI; confidence interval; D, docetaxel; DoR, duration of response; HR, hazard ratio; mo, months; NE, not evaluable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; sq, squamous; TEAE, treatment-emergent adverse event; TIS, tislelizumab Data cut-off: August 10, 2020 Citation Format: Jie Wang, Zhiyong Ma, Dingzhi Huang, Yun Fan, Xinmin Yu, Sheng Hu, Ziping Wang, Zhihua Liu, Devrim Cabuk, Mahmut Gumus, Yiyuan Ma, Yan Wang, Yan Ma, Caicun Zhou. Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced squamous (sq) non-small-cell lung cancer (NSCLC): Sub-analysis from phase 3 RATIONALE-303 randomized clinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT554.